A growth cone is the motile tip of an elongating nerve fiber, either an axon or a dendrite. Five behaviors of growth cones, migration, turning, branching, retraction and synaptogenesis, are critical in formation of neural circuits. It is important to understand how growth cones migrate and are regulated, because if growth cones fail to migrate properly during development, brain structure, and consequent behavior is abnormal. After injury to the nervous system, neural circuits are often destroyed, and if axonal growth does not occur, paralysis, memory loss, and loss of sensory function will result. A better understanding of how axons grow will help to develop strategies to promote axonal regeneration after injuries to the nervous system. The hypothesis has developed that a growth cone is a sensory-effector machine that detects relevant environmental cues and responds by regulating these critical behaviors. The implication of this hypothesis is that growth cones navigate to their targets. Our lab has examined the cellular basis of the proposed sensory-effector machinery of growth cones. We will further probe this hypothesis through experimental studies that pursue three specific aims. 1. We will use high resolution light microscopy to record the behavior of growth cones at boundaries between substrata of different compositions. We will examine filopodial and lamellipodial behavior at boundaries regulates growth cone migration. Growth cone activity at boundaries will be analyzed, and related to growth cone-substratum contacts. We will also examine whether transmembrane signalling systems mediate the regulatory effects of filopodia and lamellipodia. 2. We will purify and characterize a species of myosin I that is greatly enriched in growth cone particles from chick embryo brains. This mechanochemical enzyme may be important in the cytoskeletal activities underlying growth cone migration, turning and branching. 3. We will use three dimensional image reconstruction to examine the relationships between stable microtubules and other components of neurons and growth cones. We will examine the hypothesis that stable microtubules are critical to determining neuronal form.